This research will use behavioral, autonomic, and neuroendocrine approaches to investigate the hypothesis that neural mechanisms involving oxytocin underlie the documented association between depression and heart disease. Disorders relating to negative affect, such as depression and anxiety, are recognized risk factors for cardiovascular disease;this relationship is especially important for individuals with specific vulnerabilities (such as persons with a family history of heart disease or aging populations). Psychological and physiological responses to stressors, and in particular reactions in the social context, play an important role in the development of affective symptoms and behaviors, and have been linked directly to cardiovascular dysfunction. Furthermore, evidence indicates that oxytocin mediates behavioral and physiological processes associated with stress and social experiences, and therefore this neuropeptide may have a mechanistic role in the link between mood and cardiovascular disorders. The current research project will use a rodent model, the socially monogamous prairie vole, to study the behavioral, neuroendocrine, and autonomic responses to a social stressor (social isolation), and the potential oxytocinergic mechanisms that underlie these responses. Converging evidence suggests that the prairie vole provides a unique model system for studying responsiveness to social experiences, and that this species has utility for studying autonomic mechanisms related to mood and cardiac function. Experiment 1 will employ (a) behavioral tests relevant to depression, (b) continuous recording of autonomic and cardiac parameters, and (c) measures of circulating and central nervous system hormones and peptides, to test the hypothesis that social isolation induces behavioral and physiological responses relevant to depression and cardiovascular disease (Specific Aim 1). Experiment 2 will employ (a) chronic administration of oxytocin and (b) administration of an oxytocin antagonist, to test the hypothesis that oxytocinergic mechanisms underlie specifically the behavioral, autonomic, and neuroendocrine responses to social isolation (Specific Aim 2). This research proposes a novel mechanism by which the social environment impacts behavior, physiology, and brain function, which can promote the development of more comprehensive treatments for patients with depression and cardiovascular disease. There are important interactions among behavior, brain function, and the cardiovascular system;one such example of these interactions is the association between depression and heart disease. The current research project will investigate directly the link between these conditions by studying in an animal model the behavioral, endocrine (hormones), autonomic (control of cardiovascular function), and brain processes involved in mediating mood and cardiovascular function. This research can lead to the development of more effective treatments for patients with depression and heart disease.